This invention relates to the crystalline, substantially pure, D isomer of the sesquisodium salt of the oxa-.beta.-lactam antibiotic diacid represented by the following structural formula I, ##STR2## and to a process for the preparation thereof.
The antibiotic has been previously described, U.S. Pat. No. 4,138,486 issued Feb. 6, 1979, and is highly effective in the treatment of infectious diseases caused by both gram-positive and gram-negative bacteria. The antibiotic is one member of a class of antibiotics which have structural features in common with the cephalosporin class of antibiotics, however, they differ from the cephalosporins chemically and biologically. Structurally they differ primarily by having an oxygen atom in place of the sulfur atom of the cephalosporins. Further, the oxa-.beta.-lactams are prepared by methods differing from those by which the semi-synthetic cephalosporin antibiotics are prepared. Biologically they differ primarily from the cephalosporins by exhibiting generally high potency against pseudomonas and other gram-negative bacteria.
The compound of the formula I as the disodium salt having the D,L configuration about the chiral center in the .alpha.-carboxy-(4-hydroxyphenylacetyl side chain has been prepared previously. However, the D-epimer and a method for its preparation have thus far not been described. Further, the known preparations of the disodium salt have been non-crystalline amorphous solids with stability characteristics which render it unsuitable for pharmaceutical formulations.
The disodium salt of the D,L diacid of the formula I is formally named 7.beta.-[DL-[carboxy(4-hydroxyphenyl)acetyl]amino]-7.alpha.-methoxy-3[[(1- methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo[4.1.0]oct-2-e ne-2-carboxylic acid disodium salt. For convenience herein the disodium salt is referred to as the oxa-.beta.-lactam disodium salt and the free diacid as the oxa-.beta.-lactam diacid.
The D-epimer of the sesquisodium salt demonstrates higher antibiotic activity than the D,L-disodium salt against some organisms (e.g. E. coli).